What happened to Otto Warmbier? When the unthinkable is unknowable.

Fred and Cindy Warmbier announced June 19 that their son, Otto, had died, days after he was medically evacuated from North Korea. Here's what you need to know. (The Washington Post)

When he left the United States at the end of 2015, Otto Warmbier was a healthy, athletic 21-year-old.

When he returned last week, medically evacuated from his 17-month detention in North Korea, he was in a coma with extensive brain damage.

Warmbier died Monday, surrounded by family. His funeral will be Thursday at the high school where he graduated as salutatorian in 2013.

His death — the loss of a buoyant, hard-working, adventurous, much-loved University of Virginia student — touched off mourning, outrage and many questions. What had happened to him? And could he have been saved?

Otto Warmbier, left, with friends Emmett Saulnier and Ned Ende in May 2015 at the University of Virginia. (Sanjana Sekhar)

President Trump said Tuesday: “It’s a disgrace what happened to Otto. … And frankly, if he were brought home sooner, I think the results would have been a lot different. He should have brought home that same day. The results would have been a lot different.”

Several neurologists agreed that there is no way to know for certain what caused Warmbier’s coma — it could have been anything from an allergic reaction to a drug overdose to strangulation or some other kind of torture.

And they agreed that if that trigger could have been avoided, minimized or treated properly at the time, or if he could have been evacuated to the United States immediately after it happened, the outcome might have been very different.

Once days or weeks had passed, though, if the injury were severe, it is likely that the damage was done, some said.

But without knowing what happened to cause that, said Kevin Sheth, chief of the Division of Neurocritical Care and Emergency Neurology at Yale School of Medicine and Yale New Haven Hospital, it’s difficult to know for sure.

“Could they have tortured him, could they have given him narcotics or other medication that could have stopped his heart? Medical condition? An overdose? Some kind of toxin, a poison? Drowning?” In some of the possible situations, “an hour or two later, more or less, the course would be sealed. In another array, trauma for example, maybe there was a wide array of possible paths.”

Last week, doctors at the University of Cincinnati Medical Center said that after examining Warmbier, they had found no obvious signs of trauma, such as fractures, and that the pattern of brain injury on magnetic resonance imaging (MRI) results appeared consistent with a cardiopulmonary arrest. They said they are not aware of anything from Warmbier’s previous medical history, before his time in North Korea, that might cause cardiopulmonary arrest.

Warmbier traveled with a tour group to North Korea on his way to a study abroad program in Hong Kong but was not allowed to leave the country. After a sham trial in 2016, he was sentenced to 15 years of hard labor. Shortly after that, apparently, he was injured. He was denied consular visits and his family had no word of him after March 2016, until they were told earlier this month that he had been in a coma for more than a year. He was medically evacuated and arrived home in Cincinnati for treatment last week.

Based on what the doctors in Cincinnati had said publicly, S. Andrew Josephson, director of inpatient neurology at the University of California at San Francisco, said it seemed pretty clear that “either the brain for a period of time was not getting enough blood flow, or enough oxygen, or both. But how does that happen? … Given how young he is, it seems unlikely that this would happen spontaneously.”

“This is not a typical injury for someone that age unless there were some sort of trauma or extenuating circumstances,” said Paul Nyquist, co-director of Johns Hopkins Bayview Neurocritical Care Unit. “It seems unlikely that would happen without some form of intervention, torture of some sort.”

North Korean officials said Warmbier had contracted botulism, taken a sleeping pill, and fallen into a coma — an explanation his parents rejected.

The University of Cincinnati doctors didn’t find any evidence of botulism, but several neurologists said that doesn’t rule it out. They said it might not be possible to detect any sign of it after so many months.

If there had been botulism and he were diagnosed and treated appropriately, there would not have been brain injury, said Daniel Laskowitz, a professor of neurology at Duke University.

Sheth said “something doesn’t fit” about the botulism explanation from the North Koreans; it would require “a series of rare complications of rare things.”

Based on what the Cincinnati doctors had said publicly, Laskowitz said Warmbier was not brain dead when he returned; he could breathe on his own, despite the devastating injury. But after more than a year, he said, the chance that a patient with such an injury will regain any meaningful activity is “diminishingly small.”

Sheth said that while it might seem that a patient who is unresponsive has been in the identical state since losing consciousness, there can be a continuum. Earlier on, there may be an improved state of awareness, followed by ongoing deterioration.

Sheth said that when patients are unresponsive — as Warmbier was — doctors can only infer what they are able to experience. Recent studies have suggested that even when patients don’t show a physical response, sophisticated medical imaging can show brain activity suggesting a response to stimuli.

“Maybe he did have an awareness,” Sheth said. “It gets to the issue of suffering.”

Or of relief. On Monday, Fred and Cindy Warmbier said in a statement: “When Otto returned to Cincinnati late on June 13th he was unable to speak, unable to see and unable to react to verbal commands. He looked very uncomfortable — almost anguished. Although we would never hear his voice again, within a day the countenance of his face changed — he was at peace. He was home and we believe he could sense that.”

Last week, Warmbier was in stable condition and had no signs of infection or dysfunction of other major organs.

It doesn’t seem unusual that Warmbier died soon after his return, Nyquist said.

There could be several possible causes in such cases; sometimes an infection such as sepsis will develop which becomes fatal; sometimes family will make a difficult choice not to continue aggressive treatment; sometimes blood clots develop in people who are immobile, which can be deadly if they move to the lungs.

The Hamilton County Coroner’s Office received Warmbier’s body Monday and began an investigation into the cause of death. An autopsy will not be performed, however, because the family objected to it, said John Hatfield, an investigator with the office. The family did not give a reason for that objection, he said. “It’s just a decision the family can take, just due to him being in the hospital so long and the amount of records we did have and do have. We granted them the objection. We honored it.”

In addition to the external exam that was done, investigators are reviewing medical records from the University of Cincinnati Medical Center and the air ambulance service which transported him from North Korea, and having extensive conversations with his treating physician. Interviews and review of medical imaging and records is continuing, but they hope to have determined a cause of death soon, Hatfield said.

So what happened to Otto Warmbier?

“It’s almost a moot point,” Laskowitz said. “Whatever they did to him — they took a healthy kid, put him under horrible conditions, mental and physical anguish. … they left him at risk, didn’t treat him properly, didn’t tell anyone —

“Whatever the proximal cause was, is not even that relevant.”

Many national leaders seemed to agree. Sen. John McCain (R-Ariz.) called it murder. Sen. Benjamin L. Cardin (D-Md.) said, “Otto is dead because of Kim Jong Un’s repressive, murderous regime.”

Todd Siler, who taught Warmbier in high school, said his youngest daughter, a sixth-grader, watched the doctors talking last week about Warmbier, who had been her swimming coach. The two of them were close; Warmbier loved that every time she surfaced through the water, she had a big, spontaneous smile on her face, Siler said, and used to tease her, warmly, about that.

She came back downstairs after going to bed that night to ask Siler a question: “Can fear cause a heart attack?”

He told her, ” ‘You know honey, we’re never gonna know. There are questions that we will never be able to answer.’

“Maybe we get to invent a narrative there,” he said later. “I like to think of Otto as so strong that they couldn’t break him. They had to do things to him because they were angry.

“You’ve got to look for some way of finding comfort, I suppose.”

Students and community members gathered in the amphitheater Tuesday evening for a candlelight vigil in memory of Otto Warmbier pic.twitter.com/Gtu0JaR7mK